The Neonatal Society Summer Meeting John McIntyre ... Neonatal Society Summer Meeting John McIntyre...

The Neonatal Society Summer Meeting

John McIntyre Conference Centre

Pollock Halls, Edinburgh

June 27th – 28th 2013

The Neonatal Society Summer Meeting John McIntyre Conference Centre, Pollock Halls, Edinburgh

27th-28th June 2013 Day 1, Thursday 27

th June

12.00 – 13.30 Registration, lunch and exhibits Session 1: Chair: Dr Matthew Hyde 13.30 Welcome from meeting organiser Dr James Boardman 13.35 Cally Tann, London School of Hygiene & Tropical Medicine

Perinatal Risk Factors for Neonatal Encephalopathy in Uganda: The Role of Materno-Fetal Infection/Inflammation

13.50 Alison Howell, St Michaels Hospital Bristol, University Hospital of Bristol NHS Trust

Chorioamnionitis and Respiratory Outcome in very low birthweight infants who received Antenatal Corticosteroids

14.05 Shalini Ojha, Early Life Nutrition Research Unit, Academic Child Health, University of

Nottingham Maternal Nutrient Restriction in early to mid gestation enhances adipose tissue development in fetal lamb

14.20 Keynote Speaker: Prof Pat Monaghan, Professor of Animal Ecology, College of

Medical, Veterinary and Life Sciences, University of Glasgow Growing up and growing old: effects of developmental conditions on health in later life

15.00 Tea break, poster viewing and exhibits Session 2: Chair- Prof Neena Modi, President of the Neonatal Society 15.30 Guillermina Girardi, MRC/University of Edinburgh Centre for Reproductive Health

Statins prevent fetal cortical brain abnormalities in preterm fetuses in mice 15.45 Jane Hassell, Institute for Women’s Health, University College London

Cerebral Palsy in Children presenting to Paediatric Services in Kampala, Uganda: What percentage is attributed to acute Intrapartum Related Encephalopathy?

16.00 James Boardman, MRC/University of Edinburgh Centre for Reproductive Health

Common Variants in Genes associated with Schizophrenia and Lipid Metabolism Modulate Brain Injury after Preterm Birth

16.15 Tizard Lecture: Prof Joy Lawn, Director of Maternal Reproductive and Child

Health Centre, LSHTM, Director of Global Evidence and Policy Saving Newborn Lives programme of Save the Children, DFID Senior Research Fellow for newborn health, Three million neonatal deaths: closing action and knowledge gaps

Social Programme: 19.00 – 20.00 Reception, the Quadrangle, Old College, University of Edinburgh 20.00 – 22.30 Conference Dinner, Playfair Library Hall. Old College, University of

Edinburgh


Day 2, Friday 28th June 08.30 – 09.00 Registration Session 3: Chair- Dr Richard Thwaites 09.00 Kevin Goss, Southampton Centre for Biomedical Research, NIHR Respiratory

Biomedical Research Unit, Southampton Choline Metabolism and the Phosphatidylethanolamine N-Methyltransferase (PEMT) Pathway in newborn preterm infants

09.15 Hannah Oliver, University Of Southampton, Faculty of Medicine

The Profiling of Urinary Phospholipids and Choline Metabolites in the preterm neonate. 09.30 Matthew Hyde, Section of Neonatal Medicine, Imperial College London, Chelsea and

Westminster Hospital campus, London Mode of Delivery and offspring Body Mass Index Z-Score in Childhood: A Systematic Review and subject level Meta-Analysis of International Data

09.45 Mark Johnson, NIHR Southampton Biomedical Research Centre, University Hospital

Southampton Standardising Preterm Infant Nutrition – Optimising nutrition and growth in preterm infants using an evidence-based complex intervention

10.00 Sarah Bates, School of Clinical Science, University of Bristol, Neonatal Intensive Care

Unit, Southmead Hospital, North Bristol NHS Trust, Bristol Retrospective cohort study of early Superior Vena Cava Flow and development of Intraventricular Haemorrhage in extremely preterm infants

10.15 Cristine Sortica da Costa, Neonatal Unit, The Rosie Hospital, Cambridge University

Hospitals NHS Foundation Trust Defining Optimal Blood Pressure based on a novel cerebrovascular regulation index in preterm infants

10.30 Coffee Break, poster walk, exhibits Session 3b: Poster walk led by Prof Howard Clark during this extended coffee break 10.40 Andrew Cooper, NICU, Royal Hospital for Sick Children, Glasgow

A Comparison between a Human Milk Analyser and established laboratory methods for measurement of human milk macronutrient content

10.45 Sarah Davidson, The London Neonatal Transport Service Hypoxic Respiratory Failure in Term and Near Term Newborns: Perspective from the

Neonatal Transfer Service 10.50 Paula Midgley, University of Edinburgh, and Lothian University Hospitals NHS Trust

The Effects of Antenatal Steroids on morning Cortisol at 7 years of age 10.55 Bhavin Kawa, The London Neonatal Transport Service Bilious Vomiting in Newborns: Implications for a Neonatal Transfer Service 11.00 David Todd, Australian National University Medical School, Woden, ACT, Australia

CeasIng Cpap At standarD criteriA (CICADA): Why infants fail to come off CPAP immediately

11.05 Mary Pedley, NeTS Solent, Portsmouth Hospitals NHS Trust, Portsmouth

What Proportion of Transfers is ‘Time Critical’ and are we mobilising quickly enough?


Day 2, Friday 28th June, continued. Session 4: Chair – Dr Helen Budge 11.15 Chinthika Piyasena, Endocrinology Unit, BHF/Centre for Cardiovascular Science,

Queen’s Medical Research Institute, Edinburgh Fetal Growth associates with altered expression of imprinted genes in the placenta

11.30 Jane Hassell, Institute for Women's Health, University College London

Cell Death and Microglial Activation in the Newborn Piglet following a short period of Isoflurane anaesthesia

11.45 Prize Giving – Best Oral Presentation and Best Poster by Trainees 11.50 Young Investigator Prize Lecture: Dr David J Carr, Prenatal Cell & Gene Therapy

Group, UCL Institute for Women’s Health Somatotrophic Effects of Prenatal Ad.VEGF Gene Therapy in the Growth-Restricted Sheep Fetus and Neonate

12.20 – 13.30 Lunch, poster viewing and exhibits Session 5: Chair – Dr James Boardman 13.30 Prashanth Bhat, Division of Asthma, Allergy and Lung Biology, King's College London,

London Proportional Assist Ventilation in very prematurely born infants with evolving Bronchopulmonary Dysplasia

13.45 Divyen Shah, Royal London Hospital, London

Electrographic Seizures are associated with Brain Injury in neonates undergoing Therapeutic Hypothermia after perinatal Hypoxia-Ischaemia

14.00 Keynote Speaker: Prof Peter Ghazal, University of Edinburgh

What can systems biology tell us about neonatal sepsis? 14.40 – 15.30 Tea, poster viewing and exhibits 15.30 Close of meeting

Abstracts for

Oral Presentations

(please turn to back for

poster abstracts)

Title (Upper case)

PERINATAL RISK FACTORS FOR NEONATAL ENCEPHALOPATHY IN UGANDA: THE ROLE OF MATERNO-

FETAL INFECTION/INFLAMMATION

Authors (Presenting author underlined. If no author is a Society member please provide the name of the member introducing the author to the Society)

C Tann1,2,3

, M Nakakeeto, JJ Kurinczuk4, ED Mutuuza

5 ,P Nkurinziza

3, B Willey

1, F Cowan

6 F Namiiro

5, K.

Harris7, N. Klein

7, M. Sewebaga

5, N. Sebire

7, AM Elliott

1,3, NJ Robertson

2

Corresponding author e-mail address: [email protected]

Institution(s)

London School of Hygiene & Tropical Medicine (LSHTM)1, University College London (UCL), Institute for

Women’s Health2 MRC/UVRI Uganda Research Unit on AIDS

3 NPEU, Oxford University

4 Mulago Hospital

5

Imperial College, London6 UCL, Institute for Child Health

7

Introduction (include hypothesis)

Globally one quarter of neonatal deaths are related to perinatal asphyxia with survivors of the ensuing encephalopathy commonly developing sequelae, including cerebral palsy and seizures. Pre-clinical studies suggest that existing infection/inflammation may significantly increase the susceptibility of the developing brain to injury(1). We hypothesise that placental infection/inflammation significantly increases newborn susceptibility to brain injury and contributes to the pathogenesis of neonatal encephalopathy (NE) and poor outcome in low income settings.

Methods (include source of funding and ethical approval if required)

Ethical approval was granted by IRB approved local and national ethics committees (UK & Uganda). Between Sept’11 and Oct’12 we recruited all 210 term infants with NE (defined as a Thompson score >5) and 420 randomly sampled unaffected term infants, to an unmatched case-control study at Mulago Hospital, Kampala, Uganda. Data from antepartum, intrapartum and postpartum periods were collected. Maternal-infant investigations to identify perinatal infection included species-specific qPCR (neonatal bacteraemia, malaria, cytomegalovirus, herpes simplex), point-of-care testing (HIV, Syphilis) and maternal and neonatal C-reactive protein (CRP). Placentas were examined for histological chorioamnionitis/funisitis.

Results

The incidence of NE was 14.7 per 1000 live births and neonatal case fatality 34.3% (71/207). Clinical seizures affected 49.6% (104/210) of cases and 10.2% (21/206) were hypoglycaemic (<2.0mmol/L) on admission. Unadjusted risk factors from the preconception, antepartum and intrapartum periods were identified with the strongest associations seen with intrapartum complications. Real-Time PCR successfully identified bacteraemia in culture negative infants. Maternal HIV status (Odds Ratio (OR) 0.52; 95% confidence interval (CI) 0.29-0.95), prolonged rupture of membranes (OR 2.98; 95%CI 1.52-5.84), raised maternal CRP at delivery (p<0.0001), and clinical (OR 5.24; 95%CI 2.50-10.95) and histological chorioamnionitis (OR 2.38; 95%CI 0.92-6.11) were associated with NE in univariate analyses. Inflammation in the cord was associated with the highest risk of NE with a 10-fold increase in the crude odds of funisitis amongst encephalopathic infants when compared to controls (26.7% vs 3.9% respectively (OR10.5; 95%CI 3.27-33.56). For cases, funisitis was associated with a doubling of the crude odds of neonatal death (43.8% vs 21.2%, OR2.89; 95%CI 0.8-11.1).

Conclusions

Early results of this analysis suggest that perinatal infection/inflammation, and in particular fetal infection and inflammatory response, are important risk factors for neonatal encephalopathy and death in this low income setting.

References (include acknowledgement here if appropriate)

1) Eklind et al, Eur J Neurosci. 2001 Mar;13 (6):1101-6 The study is funded through the Wellcome Trust/LSHTM Clinical PhD Programme

Title (Upper case)

CHORIOAMNIOITIS AND RESPIRATORY OUTCOME IN VERY LOW BIRTHWEIGHT INFANTS WHO RECEIVED ANTENATAL CORTICOSTEROIDS


Dr Alison J Howell, Dr David Harding


Institution(s)

St Michaels Hospital Bristol. University Hospital of Bristol NHS Trust.


The respiratory outcome of those babies with histological chorioamnionitis treated with antenatal corticosteroids have not been examined in a UK population of infants born weighing <1500g. Our aim was to determine if there was any association between chorioamnionitis and adverse respiratory outcomes in our population of VLBW infants who received antenatal corticosteroids.


294 VLBW babies born in our hospital between Jan 2001 and Dec 2010 who had received antenatal corticosteroids and had placental histology performed were identified. Infant characteristics and outcomes were as described by the Vermont-Oxford data definitions. Statistical analysis was performed in SPSS, using chi square, student t-test and logistic regression where appropriate

Results

97 babies out of 294 babies (33%) had histological chorioamnionitis (58 of whom had funisitis). The presence of chorioamniionitis was associated with increased need for ventilation (85% vs 69% infants p = 0.006), diagnosis of respiratory distress syndrome (87% vs 71% p = 0.004) and need for oxygen at time of discharge (51% vs 33% p = 0.007). However the group of babies with chorioamnionitis were 2 weeks more immature than those without chorioamnionitis (mean gestational age at birth 27 wks vs 29wks, mean dif. -2.2, p<0.001) . After logistic regression to account for potential effects of gestational age the presence of chorioamnionitis was not associated with any respiratory sequel.

Conclusions

In our population of infants born <1500g and treated with antenatal corticosteroids the presence of histological chorioamnionitis is not associated with respiratory status after adjusting for earlier birth. The most significant predictor of respiratory progress is gestational age at delivery.


Title (Upper case)

MATERNAL NUTRIENT RESTRICTION IN EARLY TO MID GESTATION ENHANCES ADIPOSE TISSUE DEVELOPMENT IN FETAL LAMB

Authors

Shalini Ojha, Michael E Symonds, Helen Budge


Institution(s)

Early Life Nutrition Research Unit, Academic Child Health, University of Nottingham, NG7 2UH


Maternal nutrient restriction during pregnancy predisposes the offspring to adult obesity and the metabolic syndrome

1. Stimuli or insults during critical periods of development can “programme” the fetus and the resulting

adaptations can be detrimental in later life2. In both sheep and humans, the majority of fetal adipose tissue is

deposited during the final third of gestation and maternal nutritional manipulation induces differential changes in adipose tissue dependent on its timing during fetal development

3. In sheep, maternal nutrient restriction between

80 -110 days of gestation enhances fetal fat deposition. In this study, we hypothesised that maternal nutrient restriction in early to mid gestation would increase the abundance of uncoupling protein 1 (UCP1) and upregulate the expression of key transcription factors involved in brown adipogenesis in pericardial adipose tissue of fetal lamb.


Pregnant sheep were randomised to be fed 100% of total metabolisable energy (ME) requirements throughout pregnancy (C) or nutrient restriction (NR) to be fed 60% of this amount between 80-110 days of gestation. Nutrition was restored to 100% of total ME for the remaining gestation. At 140 days gestation (term = 145 days), sheep were humanely euthanased and fetal lambs sampled. All procedures were conducted with Home Office Approval under UK legislation. Gene expression for adipose tissue related genes such as CEBPβ

4 a key

transcription factor in brown adipogenesis and BMP45 a promoter of white adipogenesis were determined by

qPCR and protein analysis was performed by Western blotting and densitometry. Statistical analysis was performed using SPSS (Version 21).

Results

Maternal nutrient restriction did not affect the body weights of the mothers or the fetus but offspring of NR

mothers had significantly more pericardial adipose tissue than the offspring of C mothers (C: 3.86 0.38; NR:

4.95 0.46 g (p<0.05)). Both gene expression and protein abundance of UCP1 was significantly increased in

fetal offspring following maternal NR (Gene expression: C: 1.00 0.34; NR: 2.59 0.50 a.u. (p<0.01); Protein

abundance: C: 0.93 0.06; NR: 1.36 0.08 a.u. (p<0.05)). Gene expression of transcription factors CCAAT-

enhancer binding protein (CEBPβ) (C: 1.00 0.20; NR: 2.02 0.36 a.u. (p<0.05)) and bone morphogenetic

protein (BMP) 4 (C: 1.00 0.27; NR: 2.06 0.43 a.u. (p<0.05)) were also significantly upregulated in offspring of

NR mothers. There was no difference in either the gene expression of leptin, adiponectin, the glucocorticoid receptor or the abundance of cytochrome c and voltage dependent anion channel (VDAC).

Conclusions

Increase in pericardial adipose tissue deposition with this modest maternal nutrient restriction in is in keeping with previous studies which demonstrated increased fat deposition in other visceral depots

6 and the increase in

UCP1 signifies that development of fetal brown adipose tissue is enhanced when maternal nutrition is restricted in early to mid gestation. The upregulation of expression of these genes indicates that adipogenesis of both brown and white lineage is enhanced after maternal nutrient restriction. These latest findings further support our hypothesis that maternal nutrient restriction during gestation can programme adipose tissue development in the fetus and are in keeping with human epidemiological data suggesting that maternal malnutrition during gestation may permanently affect adult health without affecting the size of the baby at birth and that adaptations that enable the fetus to continue to grow may have adverse consequences for health in later life.


1. Barker et al. (1986) Lancet 1:1077-81. 2. Lucas (1991). Ciba Found Symp 156:38-50. 3. Budge et al.(2004) Biol Reprod. 71:359-65. 4.Kajimura et al.(2010) Cell Metab. 11: 257-62. 5.Bowers et al.(2007) Cell Cycle. 6: 385-9.4.Gopalakrishnan et al.(2001) Early Hum Dev. 63:58-9.

Title (Upper case)

STATINS PREVENT FETAL CORTICAL BRAIN ABNORMALITIES IN PRETERM FETUSES IN MICE

Authors (Presenting author underlined. If no author is a Society member please provide the name of the member introducing the author to the Society) Introduced by Dr James Boardman. Silvia Pedroni

1, Maurits Jansen

2, Ross Lenner

2, Jean Wade

1 and Guillermina Girardi

1,2.


Institution(s)

1MRC Centre for Reproductive Health,

2BHF/University Centre for Cardiovascular Science,

3MRC Centre for

Inflammation Research University of Edinburgh, UK


Premature babies are particularly vulnerable to brain injury. In this study we focus on cortical brain damage that can result in the long-term cognitive, behavioural, attentional or socialization deficits. We tested the hypothesis that complement activation plays a role in the cortical brain abnormalities in foetuses born preterm in a mouse model of inflammation-induced preterm labour. We also investigate potential treatments to prevent foetal cortical brain abnormalities and preterm birth.


We used a mouse model of inflammation-induced preterm birth (PTB) that resembles the spontaneous PTB clinical scenario. We also studied isolated foetal cortical neurons in culture. Non-invasive proton magnetic resonance spectroscopy (1HMRS) was used to study in vivo foetal brain metabolism in uterus. BOLD imaging was used to measure brain oxygenation. We detected complement C3 deposition by MRI in the foetal brains with antiC3 antibodies conjugated with superparamagnetic iron oxide (SPIO) particles. All mouse studies were conducted in accordance with Home Office welfare and ethical regulations. Results

Increased C3 deposition and increased C5a levels were observed in foetal brains in PTB compared to age-matched control. Disruption of cortical dendritic and axonal cytoarchitecture was observed in PTB-mice. Genetically deletion of C5aR and treatment with anti-C5 antibody prevented cortical foetal brain injury in PTB-mice. Fetal cortical neurons exposed to C5a showed increased glutamate (Glu) release ((nmol/ml) (5.94±0.7 vs 2.93±0.6 in untreated cells) and abnormal development and survival in vitro. Blockade of C5aR and Glu receptor restored neurons growth and survival in these cells. MRI studies showed decreased oxygenation and increased Glu levels in PTB-foetuses compared to age-matched controls (1HMRS :Glu/tCR (ppm): 1.49±0.32 vs 1.00±0.16 ppm). Simvastatin and pravastatin prevented cortical foetal brain developmental and metabolic abnormalities -in vivo and in vitro. Statins also prevented myometrial contractions that contribute to brain damage by reperfusion–ischaemic episodes. Akt/PKB signaling pathways played a role in the neuroprotective effects of statins.

Conclusions

This study shows that complement activation plays a crucial role in cortical foetal brain injury in PTL and suggests that complement inhibitors and statins might be good therapeutic options to improve neonatal outcomes in preterm birth. Clinical trials should be organized to confirm these studies in humans.


This work was supported by the Jennifer Brown Research Fund.

Title (Upper case)

CEREBRAL PALSY IN CHILDREN PRESENTING TO PAEDIATRIC SERVICES IN KAMPALA, UGANDA: WHAT PERCENTAGE IS ATTRIBUTED TO ACUTE INTRAPARTUM RELATED ENCEPHALOPATHY?


Jane Hassell1, Cally Tann

1,2, Mary Nakibirango

3, Margaret Masoke

3, Richard Idro

3,4, Nicola J Robertson

1


Institution(s)

1Institute for Women’s Health, University College London;

2London School of Hygiene and Tropical Medicine;

3Makarere University College of Health Sciences;

4Nuffield Centre for Tropical Medicine, Oxford University


Worldwide an estimated 200 million children are disabled, including those with cerebral palsy (CP); 80% live in low-income countries. Large cohort studies in high-income countries attribute 80% of CP to antenatal causes (1). These data are difficult to obtain in resource-poor settings where the proportion of intrapartum events is higher, with an estimated 1 million survivors of neonatal encephalopathy developing cerebral palsy and other neurological sequelae every year (2). We hypothesised that intrapartum events and neonatal encephalopathy would be a major contributor the aetiology of CP in a sub-Saharan Africa setting and investigated the aetiological distribution of CP in affected children presenting to Mulago Hospital, Kampala, Uganda.


Ethical approval was granted by Mulago Hospital, Uganda National Council of Science and Technology and UCL. Seventy-four children with CP presenting over a 6-week study period were recruited from all in- and out-patient Paediatric services at Mulago, a tertiary referral hospital. Consent was sought. Assessment involved (i) Detailed retrospective history obtained from the mother or primary caregiver, including any self-identified antecedents to the onset of motor impairment; and (ii) Neurological examination to describe the pattern of cerebral palsy and assign a Gross Motor Function Classification System score. Neuroimaging was not available.

Results

Conclusions

In this retrospective questionnaire-based study, 70% of mothers attributed their child’s CP to intrapartum events and/or neonatal encephalopathy. Although a single tertiary centre study and not a population based study, these data contrast with the estimated 10% of CP due to intrapartum events in high-income country population studies (1). Intrapartum and newborn care are key priorities for the prevention of CP in this resource-poor setting.


1. Blair E, Watson L. Seminars in Fetal and Neonatal Medicine. 2006; 11: 116-125. 2. Lawn JE et al., Bull WHO 2005; 83: 409-417

Check box if presenting author is a trainee: basic science trainee clinical trainee

All authors have approved the abstract, actual or potential conflicts of interest have been declared to the meetings secretary, and the abstract has not been presented previously:

Senior author supporting presentation on day of meeting: Professor Nicola J Robertson

Attributed cause N (%)

Peripartum history consistent with NE NE plus suspected infection

52 (70) 24 (32)

Neonatal infection, well at birth 2 (3)

Neonatal jaundice 6 (8)

Preterm 1 (1)

Other neonatal illness 4 (5)

Post-neonatal CNS infection 6 (8)

Unknown 6 (8)

Mean age was 25.4 months; 58% were aged <2 years (mean 9.7m). Fifty-one percent were new to Paediatric services (mean 24.1m); 49% were attending follow-up (mean 26.7m). According to maternal report 93% of infants were born at term. Overall, 49% had spastic quadraplegia; 3% spastic diplegia; 8% hemiplegia; 9% choreoathetoid; 8% hypotonic, 22% mixed pattern impairment. 70% of mothers gave a peripartum history consistent with neonatal encephalopathy (NE) and 83% attributed CP to illness in the newborn period.

Title (Upper case)

COMMON VARIANTS IN GENES ASSOCIATED WITH SCHIZOPHRENIA AND LIPID METABOLISM MODULATE BRAIN INJURY AFTER PRETERM BIRTH


JP Boardman1, A Walley

2,3, G Ball

4, P Takousis

2, ML Krishnan

4, L Hughes-Carre

5, P Aljabar

4, A Serag

6, C

King5, N Merchant

4, L Srinivasan

5, P Froguel

2,8, J Hajnal

4, D Rueckert

7, SJ Counsell

4, AD Edwards

4.


Institution(s) 1MRC / University of Edinburgh Centre for Reproductive Health,

2Genomics of Common Disease, Imperial College,

3Molecular Genetics and Genomics, Imperial College,

4Centre for the Developing Brain, King’s College London,

5Paediatrics,

Imperial College, 6Children’s National Medical Center, USA,

7Computing, Imperial College,

8Lille 2 University, France.


Adverse neurodevelopmental outcome after preterm birth is strongly associated with a phenotype that combines: cognitive dysfunction and special educational needs; altered early brain growth; and cerebral white matter injury. This is only partly explained by environmental stresses. Based on studies of the imaging and clinical phenotype we hypothesized that the development of preterm cerebral injury could be related to selected genes involved in white matter development or human cognition and behaviour.


We collected genomic DNA and magnetic resonance (MR) images from 83 preterm infants. NRES approval was obtained. Genotyping was performed using the Sequenom i-PLEX assay and MALDI-TOF mass spectrometry. Images were acquired at mean postmenstrual age 40

+2 weeks. We used Tract Based Spatial Statistics (TBSS)

and Deformation Based Morphometry (DBM) to examine the risks conferred by carriage of particular alleles at tag single nucleotide polymorphisms (SNPs) in a restricted number of genes and related these to the preterm cerebral endophenotype. Type 1 error was controlled using the q-value algorithm (false discovery rate 0.05)

1.

Results

Thirty-five tag SNPs across 13 genes were tested. After correcting for prematurity and age at scan, we found that carriage of the minor allele (G) at rs2518824 in the armadillo repeat gene deleted in velocardiofacial syndrome (ARVCF) gene, which has been linked to neuronal migration and schizophrenia, was associated with reduced FA in the corpus callosum, the superior corona radiata, the fornix, and the centrum semiovale (p=0.0009). Carriage of the minor allele (A) at rs174576 in the fatty acid desaturase 2 (FADS2) gene, which encodes a rate-limiting enzyme for endogenous long chain polyunsaturated fatty acid synthesis and has been linked to intelligence, was associated with reduced FA in the corona radiata (p=0.0019). None of the remaining 33 tag SNPs were associated with FA changes after correction for multiple tests. SNP associated alterations in tract microstructure identified in TBSS analyses were not associated with alterations in brain morphology assessed by automatic segmentation of tissue compartments.

Conclusions

These results suggest that: genetic variants modulate white matter injury after preterm birth; and known susceptibilities to neurological status in later life may be exposed by the stress of premature exposure to the extra-uterine environment.

References (include acknowledgement here if appropriate) 1Storey JD, Tibshirani R. PNAS 2003 Aug 5;100(16):9440-5.

Primary funding: NIHR BRC funding scheme.

Title (Upper case)

CHOLINE METABOLISM AND THE PHOSPHATIDYLETHANOLAMINE N-METHYLTRANSFERASE (PEMT) PATHWAY IN NEWBORN PRETERM INFANTS


Kevin CW Goss 1,2,3

, Victoria M Goss 1,2

, J Paul Townsend 1, Ranjit Gunda

3, Jane Rhodes-Kitson

1, Richard

Thwaites 4, Howard W Clark

1,2,3, Anthony D Postle

1,2


Institution(s)

1 Southampton Centre for Biomedical Research, NIHR Respiratory Biomedical Research Unit, Southampton, UK

2 Division of Clinical Experimental Science, Faculty of Medicine, University of Southampton, Southampton, UK

3 Princess Anne Hospital, Southampton, UK

4 Queen Alexandra Hospital, Portsmouth, UK

4 Queen Alexandra Hospital, Portsmouth, UK


In adults the essential nutrient choline is important as a substrate for the production of phosphatidylcholine (PC) phospholipids and as a significant methyl donor. Previous studies have shown that the phosphatidylethanolamine N-methyltransferase (PEMT) pathway, located specifically within hepatocytes, synthesises predominantly polyunsaturated PC species

a and can produce choline de novo

b. To date the role of

this pathway and the metabolism of this important substrate has not been investigated in the preterm infant.


Newborn premature infants (≤28+6

weeks) were recruited within 48 hours of birth. Lipid extracts from sequential plasma samples were then analysed by tandem electrospray ionization mass spectrometry (ESI MS/MS) and liquid chromatography multiple reaction monitoring tandem mass spectrometry (LC-MRM MS/MS) to monitor the incorporation of a short single IV infusion of methyl-D9 labelled choline (D9C) into the plasma choline pool and the phosphatidylcholine (PC) species. The incorporation into newly synthesized PC molecular species can then be monitored over time and directly reflects in vivo synthesis and secretion. (Local REC approval 09/H0502/95)

Results

In this study population the enrichment of choline by D9C in plasma decreases rapidly over the first 24 hours

following infusion. The newly synthesised phospholipids produced via the PEMT pathway are predominantly

mono- (PC16:0/18:1) and di-unsaturated (PC16:0/18:2) species but the pathway remains an important source of

polyunsaturated PC species. Using multiple isotopomer distribution analysis (MIDA) the maximal synthetic rate

of flux through the PEMT pathway is calculated to be 0.06%, significantly lower than reported in adult volunteers

(0.53%).

For the first time this study demonstrates that the activity of the hepatic PEMT pathway is significantly reduced when compared to adults despite rapid choline metabolism.

Conclusions

PEMT is vital as a source of de novo choline production and for the polyunsaturated phospholipid species. This study demonstrates for the first time that preterm infants are especially vulnerable to inadequate choline intake or deficiency and may have implications for recommended levels of choline supplementation in this population.


a. PYNN, C.J., et al. 2011. Specificity and rate of human and mouse liver and plasma phosphatidylcholine synthesis analyzed in vivo. J Lipid Res, 52, 399-407, b. JACOBS, R., et al. 2010. Impaired de novo choline synthesis explains why phosphatidylethanolamine N-methyltransferase-deficient mice are protected from diet-induced obesity. J Biol Chem, 285, 22403-13

Title (Upper case)

THE PROFILING OF URINARY PHOSPHOLIPIDS AND CHOLINE METABOLITES IN THE PRETERM NEONATE.


H.L. Oliver, V.M. Goss, J. Rhodes-Kitson, J.P. Townsend, J. Brandsma, R. Gunda, H. Clark, K.C.W. Goss, A.D. Postle.


Institution(s)

University of Southampton, Faculty of Medicine NIHR Respiratory BRU, Southampton


A previous study using an infusion of methyl-D9 choline (a stable isotope label) given to ventilated preterm

neonates has successfully investigated phosphatidylcholine (PC) kinetics in endotracheal aspirates and plasma.

We have now analysed metabolites and PC found in the urine of these individuals to investigate for the first time

postnatal renal-specific handling of lipids in the preterm neonate. We hypothesise that time-dependent changes in

the lipid and metabolite profile demonstrate the transition between pre- and postnatal function and renal maturation

over the first 10 days of life.


Labelled methyl-D9 choline infusions were administered to consented preterm neonates within 48 hours of birth. Infants who remained ventilated were given a second methyl-D9 choline infusion 120 hours after recruitment. Lipid extracts and aqueous phase aliquots from urine samples at specific time points after infusion were analysed using electrospray ionisation tandem mass spectrometry (ESI MS/MS) and ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) respectively.

Results

There is a mixture of mono-, di- and polyunsaturated PC species present in the urine. Compared to other species, there is more endogenous and newly synthesised urinary PC16:0/18:1, but there is a lack of polyunsaturated species in the urine. Maximal label enrichment of urinary phosphatidylcholine (PC) species occurs at 24 hours after each methyl-D9 choline infusion but rates of enrichment decrease slowly and remain more constant than previously demonstrated in plasma. Endogenous urinary PC concentrations decrease over time and newly synthesised lysospecies were not detectable in analysed samples. There is rapid fractional label incorporation into the choline and betaine pools, as previously seen in plasma, with significant increases in incorporation after the second infusion of labelled choline at 120 hours (P=0.001). Concentrations of urinary choline and betaine also decrease over time.

Conclusions

This study is the first demonstration of the profiling of choline metabolites and PC kinetics in the urine of preterm

neonates. It demonstrates that the powerful methyl-D9 choline labelling technique can be used to model tissue-

specific PC kinetics throughout the body. We have demonstrated time-dependent alterations to the profile of PC

and choline metabolites in the urine, suggesting rapid changes in postnatal renal PC metabolism. This is

independent of plasma metabolism, which probably reflects PC synthesis and secretion by the kidney as it

matures and adapts to postnatal function.


Goss KCW. PhD Thesis, University of Southampton, 2012.

Title (Upper case)

MODE OF DELIVERY AND OFFSPRING BODY MASS INDEX Z-SCORE IN CHILDHOOD: A SYSTEMATIC

REVIEW AND SUBJECT LEVEL META-ANALYSIS OF INTERNATIONAL DATA


Hyde MJ, Darmasseelane K, Gale C, Santhakumaran S, Modi N on behalf of the “Mode of delivery and offspring BMI” study group*


Institution(s)

Section of Neonatal Medicine, Imperial College London, Chelsea and Westminster Hospital campus, 369 Fulham Road, London, SW10 9NH, UK


We have previously suggested that mode of delivery is a plausible determinant of life-long health, with exposure to normal labour and/or vaginal microbial initiating key metabolic and immune trajectories (1). Here we present preliminary results of a systematic review and meta-analysis of subject-level data to test the hypothesis that there is a statistically significant and clinically relevant difference in offspring Body Mass Index (BMI) z-score in childhood in relation to mode of delivery.


A literature search was conducted in Pubmed using pre-defined search terms, following a registered protocol. Inclusion required that the study reported (a) mode of delivery and childhood BMI (b) mode of delivery with long-term offspring follow-up or (c) offspring BMI in childhood with birth characteristics. Reference lists were hand-searched for further potential studies. Authors were contacted to obtain subject level data on outcomes of interest. BMI z-score was calculated using the International Obesity Task Force criteria. A meta-analysis was carried out in RevMan5 using the inverse variance method and random effects models. Subgroup analyses were used to explore differences between Vaginal Delivery (VD) and either emergency/in-labour Caesarean Section (IL-CS) and elective/pre-labour CS (PL-CS). Results are presented as mean difference [95% confidence interval].

Results

Data were obtained from 21 international studies (631,427 subjects; of which 96,740 were CS deliveries). The mean difference in BMI z-score between CS and VD groups was 0.12 [0.09, 0.16] (p<0.0001). Data from 8 studies (167,847 subjects) were suitable for inclusion in the subgroup analysis; mean difference in BMI z-score comparing IL-CS with VD 0.07 [0.04, 0.10] (p<0.0001); 0.03 [-0.01, 0.07] comparing PL-CS and VD.

Conclusions

Using individual data from over half a million children we identify an association between CS and increased offspring BMI z-score in childhood. This is in keeping with our previous report of a significant difference in BMI between adults born by CS or VD (2). The implication of a possible difference between type of CS is uncertain and it is important to note that the association between mode of delivery and offspring outcome is liable to confounding. We aim to explore these aspects, including adjusting for potential confounders to further address the possibility that mode of delivery affects life-long health.


(1) Hyde MJ, et al (2012) Biological Reviews 87:229-243. (2) Darmasseelane K, et al (2012) Summer Meeting of the Neonatal Society. *Members of the Mode of delivery and offspring BMI study group: Ajslev TA, Barros F, Bhattacharya S, Castro-Rodriguez J, Cohn BA, Crume T, Eriksson J, Friedlander Y, Gissler M, Harlap S, Hartikainen JA-L, Huh S, Inskip H, Jarvelin M-R, Li H, Liu J, Nohr EA, Osmond C, Pouta A, Smith KR, Sorensen TIA, Svensson J, Teyhan A, Wijga A,Yajnik C, Zhou Y.

Title (Upper case)

STANDARDISING PRETERM INFANT NUTRITION – OPTIMISING NUTRITION AND GROWTH IN PRETERM

INFANTS USING AN EVIDENCE-BASED COMPLEX INTERVENTION


Mark J Johnson1, 2

, Jenny P Pond1, 2

, Freya Pearson2, Anita Emm

3 and Alison A Leaf

1, 2


Institution(s)

1.NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust 2.Department of Neonatal Medicine, University Hospital Southampton NHS Foundation Trust, Southampton, UK 3.Department of Nutrition and Dietetics, University Hospital Southampton NHS Foundations Trust, Southampton


Postnatal growth failure is common in preterm infants and is associated with adverse neurodevelopmental outcomes[1]. One reason for poor growth is that nutritional care is often variable and nutrient intakes suboptimal, despite increasing literature regarding best practice in this area. Optimising nutrient intakes has the potential to improve both growth and developmental outcomes.


We developed an evidence-based, complex intervention to improve the nutritional care of preterm infants and introduced this in stages. Stage one (Aug–Dec 2011) included improved parenteral nutrition solutions, multi-disciplinary nutrition team and staff education sessions. Stage two (Jan-Dec 2012) included nutrition guidelines, screening tool and ‘nutrition nurse champions’. Data on nutrient intakes and growth were collected on infants less than 30 weeks or 1500g at birth during each period, and compared with a pre-intervention cohort born during 2009. Differences between periods were analysed by ANOVA with Tukey’s method (Stata v12.1).

Results

2009 (n=65) 2011 (n=36) 2012 (n=75)

Energy 89.1 (18.6) 94.7 (19.6) 96.7 (18.4)* Protein 66.9 (20.5) 75.4 (19.5) 78.2 (18.6)* Carbohydrate 91.1 (19.6) 93.8 (18) 95.3 (17.2) Fat 91 (23.7) 92.9 (20.3) 93.7 (19.8) Calcium 65 (23.4) 76 (20.7)* 78.6 (18.9)* Phosphorous 127.8 (123.5) 131.7 (73.9) 148.2 (148.8) Zinc 72 (17.8) 96.8 (19)* 99.7 (15.7)* Copper 133.1 (128.7) 143.6 (86.4) 156.8 (150.3) Selenium 151.8 (124.6) 154.6 (83.8) 166.1 (148.6) Vitamin A 128.7 (62.3) 111.8 (43.7) 113.4 (39.4) Vitamin D 72.1 (25.4) 107.8 (39)* 101.8 (30.1)* Vitamin E 48.3 (20.9) 64.9 (25.8)* 65.6 (22.9)*

Table 1: Mean (SD) daily nutrient intakes in 2009, 2011 and 2012 as a percentage of recommended amounts[2], *p<0.05 for difference vs 2009

For the majority of nutrients, mean daily intake (as a percentage of recommended amounts) increased across study periods, particularly for energy, protein, calcium, zinc and vitamins D and E (see table 1). Actual mean protein intakes increased from 2.45 to 2.82 and 2.94g/kg/day. Growth also improved, with the mean change in standard deviation score (SDS) for weight between birth and discharge of -0.90, -0.58 and -0.45 in 2009, 2011 and 2012 respectively (p<0.01 for difference between 2009 and 2012 only). For head circumference the mean change in SDS between birth and discharge was -0.37, -0.11 and -0.26 respectively (NS).

Conclusions

The complex intervention used in this study improved nutrient intakes and in turn resulted in improved growth, with significant improvements in weight gain and a trend towards improved head growth. This suggests that implementing evidence based practice changes can significantly improve care and outcomes.


1.Ehrenkranz, R.A., et al., Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. Pediatrics, 2006. 117(4): p. 1253-61. 2.Tsang, R.C., Nutrition of the preterm infant. 2nd. 2005, Cincinnati: Digital Educational Publishing. viii, 427 p.

mailto:[email protected]

Title (Upper case)

RETROSPECTIVE COHORT STUDY OF EARLY SUPERIOR VENA CAVA FLOW AND DEVELOPMENT OF

INTRAVENTRICULAR HAEMORRHAGE IN EXTREMELY PRETERM INFANTS.

Authors

Sarah Bates, David Odd, Richard Wach, David Evans, Axel Heep


Institution(s)

School of Clinical Science, University of Bristol, Neonatal Intensive Care Unit, Southmead Hospital, North Bristol

NHS Trust, Bristol UK


Assessment of superior vena cava flow (SVCF) on echocardiography is used to indirectly estimate cerebral

perfusion in preterm infants. Impaired cerebral perfusion is thought to be a major contributor in the pathogenesis

of intraventricular haemorrhage (IVH). Aim of the study was to look for an association between SVCF at < 24h

of age and clinical factors that contribute to the development of IVH in a cohort of patients at highest risk of

developing IVH stratified by GA less 28 weeks.


Single centre retrospective cohort study. 247 infants (23+0

-27+6

weeks GA) admitted to Southmead Hospital

tertiary NICU between 03/2008 and 01/2012 were enrolled. 109 patients had SVCF analysis and survived to 7

days. Retrospective clinical data collection, evaluation of medical history and independent re-assessment of

digitalised stored cranial ultrasound (CrUS) examinations. Calculation of SVCF was as described by Kluckow et

al. Statistical analysis using SPSS 17.0 (Student t-test; MWU test, multivariable logistic regression; ROC).

Results

The median GA of the study group was 25+4

weeks (23+2

-27+5

). 46/109 (42%) infants developed IVH defined on

CrUS at day 7 postnatal age. SVCF measured at median 8.5h of life (range 1-23h). SVCF was significant lower

(71ml/kg/min median, 30-140 ml/kg/min range) in infants diagnosed with IVH compared to infants with no IVH

(84 ml/kg/min median, 27-200 ml/kg/min range, p= 0.049). SVCF was inversely correlated to PDA size (r= -0.21:

p=0.03). Infants with IVH were born with lower GA (24+5

versus 25+6

median; p= 0.01), less antenatal steroids

(p=0.02), higher incidence of spontaneous vaginal delivery (p=0.003), elevated INR at delivery (p=0.02) and

lower platelet count at 24h of age (p=0.001). Multivariable logistic regression analysis (gender, GA, antenatal

steroids, SVCF, CRP at 24h) did not confirm independent association of SVCF at < 24h of age with development

of IVH.

Conclusions

Our study results confirm low SVCF at < 24h of life contributing to the pathophysiology of IVH in extremely

preterm infants. Early postnatal echocardiographic assessment estimating PDA shunt and SVCF is prerequisite

to balance cerebral perfusion in infants at risk of developing IVH.


Kluckow M & Evans N. Superior vena cava flow in newborn infants: a novel marker of systemic blood flow (Arch Dis Child 2000; 82: F182-F187)

Title (Upper case)

DEFINING OPTIMAL BLOOD PRESSURE BASED ON A NOVEL CEREBROVASCULAR REGULATION INDEX IN PRETERM INFANTS


CS. Costa1, S. Mitra

1, H O’Reilly

1, M. Czosnyka

2, P. Smielewski

2, J.D. Pickard

2, T. Austin

1


Institution(s)

1Neonatal Unit, The Rosie Hospital, Cambridge University Hospitals NHS Foundation Trust, UK,

2Department of

Academic Neurosurgery, University of Cambridge, UK


Defining optimal cerebral perfusion pressure, based on strength of cerebrovascular reactivity improves outcome

in adult neurocritical care1. We aimed to describe a novel index of cerebrovascular reactivity, called tissue

oxygen heart rate reactivity (TOHRx) in a cohort of preterm infants and investigate whether this index could be

used to define optimal mean arterial blood pressure (MABPOPT) in this population.


60 preterm infants born at median (range) gestational age of 26+0 (23+4 – 32+1) were studied with signed parental consent. Median (range) age at the study was 34 hours of age (5 to 228h) and median time of recorded data was 2 hours (1 - 24h). The cerebral tissue oxygenation index (TOI) was measured using the NIRO 200NX near-infrared spectrophotometer. Mean arterial blood pressure, arterial oxygen saturation and heart rate were simultaneously recorded and analysed using ICM+ software

2. Severity of clinical illness was assessed using

CRIB II score. This research project had ethical approval and was supported by Sparks3.

Results

TOHRx was calculated from moving correlation coefficient, using 5-minutes time windows between 10 seconds

average values of TOI and HR. The median (range) of TOHRx was –0.0223 (-0.4631 – 0.3218). Correlation

between TOHRx and CRIB II, assessed using linear regression analysis, was significant (R=0.35, p=0.006).

MABPOPT for individual patients was determined by dividing MABP into 2mmHg bins and averaging TOHRx

within those bins. An automatic curve fitting method was applied to determine the MABP value with the lowest

associated TOHRx value (corresponding to maximal cerebrovascular reactivity). The median (range) MABPOPT

was 34.5 (25-55). The values of MABPOPT calculated for each individual patient were used to determine the

average distance of MABP from the ‘optimal’. This measurement of divergence from MABPOPT was significantly

greater in those patients who died (4.2 +/-2.7mmHg vs 2.1 +/-1.6mmg, p=0.013 non-parametric test).

Conclusions

TOHRx is a novel index of cerebrovascular reactivity. TOHRx can be used to define a value MABPOPT; using this

methodology there was a significant deviation from MABPOPT in those infants who died. The use of TOHRx to

define MABPOPT may therefore be a valid approach to managing blood pressure in these infants.


1. Steiner LA, et al. Crit. Care Med. 2002;30:733–738. 2. Smielewski P, et al. Acta Neurochir Suppl. 2005;95:43-9. 3. Sparks – Registered Reseach Charity number 1003825.

TITLE (UPPER CASE)

FETAL GROWTH ASSOCIATES WITH ALTERED EXPRESSION OF IMPRINTED GENES IN THE PLACENTA


Piyasena C1,2

, B Khulan1, Menon G

2, Reynolds R

1, Drake AJ

1


Institution(s)

1. Endocrinology Unit, BHF/Centre for Cardiovascular Science, Queen’s Medical Research Institute, Edinburgh

2. Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh


Variability in disease risk is graded across the usual range of birth weight within the population. Imprinted genes

regulate placental and fetal growth, postnatal metabolism and are vulnerable to dosage modulation. Altered

function of imprinted genes may be one mechanism in the developmental origins of disease. We studied the

expression of candidate imprinted genes in the placenta with respect to anthropometric parameters at birth.


Placental samples for 63 term singleton infants were obtained from the Edinburgh Reproductive Tissue Bio-

Bank. Samples were chosen to represent a wide variation in birth weight. Pregnancies complicated by

congenital abnormalities or diabetes were excluded. Standard deviation scores (z scores) and percentiles were

derived from “British 1990 reference data, reanalysed 2009”1. Gene expression was analysed using real-time

PCR. Candidate reference genes were scrutinised using geNorm2 and Normfinder

3 to determine the most stable.

Results

Insulin-like growth factor 2 (IGF2) mRNA expression levels showed a positive relationship (Beta = 0.271, p =

0.029) and p57KIP2

cyclin-dependent kinase inhibitor (CDKN1C) mRNA levels showed a negative relationship

(Beta = -0.329, p = 0.008) with birth weight z score, adjusted for maternal BMI and parity using linear regression.

Five other imprinted genes H19, GRB10, ZIM2, IGF2R and PHLDA2, showed no significant relationship with

size at birth.

Conclusions

IGF2 is the major prenatal growth factor and is paternally imprinted. CDKN1C has an inhibitory effect on the cell

cycle and is maternally imprinted. As genomic imprinting is under epigenetic regulation, these are candidates for

the study of environmentally influenced non-Mendelian effects on fetal size and developmental programming.


1. LMS growth, version 2.71, 2011. http://www.healthforallchildren.co.uk/

2. http://medgen.ugent.be/~jvdesomp/genorm/ 3. http://www.mdl.dk/publicationsnorm finder.htm

2. http://medgen.ugent.be/~jvdesomp/genorm/

Title (Upper case)

CELL DEATH AND MICROGLIAL ACTIVATION IN THE NEWBORN PIGLET FOLLOWING A SHORT PERIOD OF ISOFLURANE ANAESTHESIA


J Hassell1, K Broad

1, I Fierens

1, B Fleiss

2, M Ezzati

1, G Kawano

1, A Oliver Taylor

1, I Tachsidas

1, J Rostami

1, D

Ma3, X Golay

4, P Gressens

2, G Raivich

1, R Sanders

4, NJ Robertson

1


Institution(s)

1 Institute for Women's Health, University College London,

2Centre for the Developing Brain, Kings College

London, 3Anaesthetics, Imperial College London,

4Institute of Neurology, University College London,


Anaesthetic exposure in the neonatal period is associated with pathologically increased neuroapoptosis and long-term learning impairment in rodent and non-human primate models. Maximal damage occurs at the time of peak synaptogenesis; in humans this extends for several years post-partum. A piglet model will be of strong clinical relevance as piglet brain development is similar to that of humans. We hypothesised that a 6-hour exposure to isoflurane would increase cell death and lead to inflammatory changes in the neonatal piglet brain. We investigated putative mechanisms of injury by investigating genome expression with microarray technology.


Ten male piglets aged <24 hours were assigned to 2 groups: (i) Naïve (n=5) who were euthanased immediately or (ii) Anaesthesia – induced with IM midazolam followed by tracheal intubation and 2% isoflurane and IV fentanyl for 6 hours before euthanasia (n=5). Immunohistochemistry was performed to assess cell death (TUNEL, cleaved caspase 3) and microglial activation (Iba1) in nine brain regions. Dying cells were phenotyped by double labelling caspase-positive cells with NeuN (neurons) or Olig2 (oligodendrocytes).

Results

0

2

4

6

Tu

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os

itiv

e c

ells

* *

* * * *

cng ins pyr hip ic pvwm cdt ptmn thlm

Conclusions

Six hours of isoflurane anaesthesia increased cell death and microglial activation in the newborn piglet brain; the basal ganglia and white matter appear to be particularly vulnerable. This apoptosis may relate to the suppression of neurotrophic synaptic signalling by anaesthesia exposure.


1. Sanders et al., 2013. British Journal of Anaesthesia; 29th March (e-published ahead of print)

2. Brambink et al., 2012. Annals of Neurology 72; 525 - 535

Check box if presenting author is a trainee: basic science trainee clinical trainee

All authors have approved the abstract, actual or potential conflicts of interest have been declared to the meetings secretary, and the abstract has not been presented previously:

Senior author supporting presentation on day of meeting: Professor Nicola J Robertson

Compared to naïve, 6h exposure to 2% isoflurane with ventilation and intensive physiological support was associated with an increase in TUNEL positive cells particularly in the basal ganglia and white matter (p<0.05) and a corresponding increase in caspase positive cells (p<0.05). Double labelling showed that dying cells were most often oligodendroglia. Significant microglial activation on Iba1 staining was seen in 6 of the 9 regions (p<0.05, one way ANOVA and post-hoc Tukey). Expression of 77 identified gene transcripts was significantly affected by anaesthesia; 17 were transcription factors or regulators, of which 13 were down-regulated with anaesthesia exposure.

Title (Upper case)

SOMATOTROPHIC EFFECTS OF PRENATAL AD.VEGF GENE THERAPY IN THE GROWTH-RESTRICTED SHEEP FETUS AND NEONATE Authors (Presenting author underlined)

David J Carra,b

, Raymond P Aitkenb, John S Milne

b, Vedanta Mehta

a,c, Donald M Peebles

a, John F Martin

c, Ian C Zachary

c,

Jacqueline M Wallaceb, Anna L David

a


Institution(s)

a Prenatal Cell and Gene Therapy Group, UCL Institute for Women’s Health, University College London

b Early Life Nutrition Group, Rowett Institute of Nutrition and Health, University of Aberdeen

c Centre for Cardiovascular Medicine and Biology, University College London


Fetal growth restriction (FGR) is a leading cause of perinatal mortality and is associated with considerable morbidity in

neonatal and later life. The commonest cause is reduced uterine blood flow (UBF). In normal sheep pregnancy, adenovirus

(Ad) mediated over-expression of vascular endothelial growth factor (VEGF) in the uterine arteries (UtA) increases UBF.

We hypothesised that enhancing UBF would improve fetal nutrient delivery in a sheep paradigm of FGR that is

characterised by reduced UBF from mid-gestation.


Singleton pregnancies were established using embryo transfer in adolescent ewes subsequently overnourished to induce

FGR (n=78) or control-fed (n=12). Ewes were randomised mid-gestation to receive bilateral UtA injections of 5x1011

particles Ad.VEGF-A165 or inactive treatment (5x1011

particles of control vector Ad.LacZ or saline). Fetal growth and

wellbeing were evaluated using serial ultrasound by a single operator blind to study group. Late gestation study: UtA

vasorelaxation and placental mRNA expression of various angiogenic factors/receptors were examined by organ bath

analysis and qRT-PCR, respectively. Postnatal study: Pregnancies continued until spontaneous delivery near to term (=145

days). Lambs were weighed and measured at weekly intervals, and underwent immune and metabolic challenge, dual-

energy X-ray absorptiometry (DEXA) and necropsy at 8, 9, 10 and 12 weeks of age, respectively. In both studies DNA

methylation was quantified at 59 individual cytosine-guanine (CpG) dinucleotides in 14 CpG islands in ten somatotrophic

axis genes [insulin, insulin-like growth factor (IGF)-1, IGF-2, H19, growth hormone (GH), glucocorticoid/insulin receptor

(R), GHR, IGF1R and IGFR2] in hepatic tissues using bisulphite sequencing.

Results

In both studies, ultrasonographic fetal growth velocity was increased in Ad.VEGF-A165-treated vs. control-treated

overnourished pregnancies at 3-4 weeks post-injection. At 0.9 gestation, fewer fetuses were markedly growth-restricted and

fetal brain sparing was mitigated. Ad.VEGF-A165-transduced vessels showed enhanced vasorelaxation and FLT1/KDR

expression was increased in the maternal placental compartment. Following delivery at 141±2.4 days (mean±SD, range

132–145 days) gestation Ad.VEGF-A165-treated lambs tended to be heavier (p=0.081) with increased placental efficiency

(p=0.072). There were no differences in the level of neonatal care required to ensure lamb survival or acute phase response

to immune challenge. Postnatal growth rates and glucose-stimulated insulin secretion were increased, however fractional

growth and insulin resistance were unaffected. DEXA and post-mortem analysis demonstrated increased lean tissue mass.

No epigenetic effects of Ad.VEGF-A165 were observed, but postnatally IGF-1 and insulin methylation were M>F and F>M,

respectively, and insulin gene methylation correlated with fasting plasma insulin levels.

Conclusions

Ad.VEGF-A165 safely increases fetal growth in this ovine FGR paradigm and mitigates fetal brain sparing, an adaptation

that is associated with poorer neurodevelopmental outcomes. Ad.VEGF-A165 increased UtA vascular reactivity and

upregulated maternal placental FLT1/KDR expression, suggesting that its beneficial effects on fetal growth might be

mediated at the placental level via effects on vascularity and/or nutrient transport capacity. Increased postnatal growth rates

and insulin secretion in Ad.VEGF-A165-treated lambs most likely reflects their relative size advantage at birth rather than

altered epigenetic status of key somatotrophic genes. We have recently secured funding to translate this potential therapy

into the clinic. The EVERREST consortium will complete a full reproductive toxicology package and conduct a bioethical

study and first in-woman I/IIa safety/efficacy trial of Ad.VEGF in pregnancies affected by severe early-onset FGR.

Title (Upper case)

PROPORTIONAL ASSIST VENTILATION IN VERY PREMATURELY BORN INFANTS WITH EVOLVING

BRONCHOPULMONARY DYSPLASIA


Dr P Bhat, Dr GF Rafferty, Dr S Hannam, Professor AD Milner, Professor A Greenough


Institution(s)

Division of Asthma, Allergy and Lung Biology, King's College London, London, United Kingdom


During assist control ventilation (ACV), ventilator inflations are triggered by the onset of the infant’s

respiratory efforts. Proportional assist ventilation (PAV) offers additional advantages as the ventilator

pressure is servo controlled throughout each respiratory cycle and the ventilator can reduce the

resistive and the elastic load (work of breathing) of the infant (“unloading”). Infants with evolving

bronchopulmonary dysplasia (BPD) frequently have severe lung function abnormalities and hence may

benefit more from PAV than ACV.


A randomised crossover study in prematurely born infants was undertaken. Prior to the start of

the study, each infant’s compliance and resistance were determined using the ventilator

(Stephanie paediatric ventilator, F Stephan, Gackenback Germany). During PAV, a median elastic

unloading was used that compensated for 100% of the infant’s baseline compliance. Resistive

unloading was not used as this may result in abnormal airway pressure oscillations. At the end of

an hour on each ventilator mode, the oxygenation index (OI) was calculated and measurements

were made of the PaCO2 levels, the work of breathing (assessed using the pressure time product,

PTP) and respiratory muscle strength (by assessment of the maximum diaphragmatic (Pdimax)

and the inspiratory (Pimax) and expiratory (Pemax) pressures during brief airway occlusions).

Results

Ten infants with a median gestational age of 25 (range 24-28) weeks have been studied at a

median of 43 (range 08-86) days. Their median baseline compliance was 0.6 (range 0.3-0.7)

mls/cm H2O and resistance was 86.5 (range 50-102) cmH2O/l/sec. The median OI following one

hour on PAV was significantly lower than that following one hour on ACV (5.55 (range 5-11)

versus 10.16 (range 7-16) respectively), p=0.005. There were no significant differences in Pimax

between PAV and ACV (20.33 (range 11.24 - 37.3) cm H20 versus 21.72 (range 13.61 – 38.6) cm

H20 respectively), p=0.445 nor in the PaCO2 levels (7.98 (5.72 - 10) kpa versus 7.65 (5.7 – 12.1)

kpa respectively), p=0.799. Following an hour on PAV compared to following an hour on ACV,

however, the PTP levels were lower (253 (range 59-556) cm H20/s/min versus 344 (range 55-

544) cm/H20/s/min), p=0.013, Pdimax levels were higher (44.26 (range 21-66) cm H20 versus 35

(range 19-45) cm H20), p=0.005 and Pemax levels were higher (25.67(range 6.5-42)cm H20

versus 15(range 3-35)cm H20), p=0.005.

Conclusions

These results suggest that PAV compared to ACV may be advantageous for infants with evolving BPD.


Title (Upper case)

ELECTROGRAPHIC SEIZURES ARE ASSOCIATED WITH BRAIN INJURY IN NEONATES UNDERGOING THERAPEUTIC HYPOTHERMIA AFTER PERINATAL HYPOXIA-ISCHAEMIA.


Divyen K Shah MBChB, PhD 1,2, Courtney J Wusthoff MD3, Paul Clarke MB ChB, MD4, John S Wyatt MBBS, FRCPCh5, Sridhar M Ramaiah MBBS MD4, Ryan J Dias MBBS1, Julie-Clare Becher MBChB, MD6; Olga Kapellou MRCPCH, MD7 and James P Boardman FRCPCH, PhD6,8.


Institution(s)

1Royal London Hospital, London, UK; 2Barts and the London Medical School, London, UK; 3Stanford University School of Medicine, Palo Alto, CA; 4Norfolk and Norwich University Hospitals, Norfolk, UK; 5University College London, London, UK; 6Royal Infirmary of Edinburgh, Edinburgh, UK; 7Homerton University Hospital, London, UK; 8MRC / University of Edinburgh Centre for Reproductive Health, Edinburgh, UK


Seizures are common among newborns with hypoxic-ischemic encephalopathy (HIE) but the relationship between seizure burden and severity of brain injury among neonates receiving therapeutic hypothermia (TH) for HIE is unclear. We tested the hypothesis that seizure burden is a risk factor for cerebral injury as seen on MRI in this group.


Term neonates undergoing 72 hours of TH at four centers were selected for study if they had continuous 2 channel EEG with amplitude-integrated EEG (aEEG) and MRI. aEEGs were independently analyzed for severity of background and seizure burden. MRIs were graded by the severity of injury using a system that has been shown to predictive of outcome in this group of infants (1). aEEGs and MRIs were rated independently and in a blinded fashion by two experts.

Results

Of 85 neonates, 52% had seizures on aEEG. Overall, 35% had high seizure burden, 49% had abnormal aEEG background in the first 24 hours and 36% had severe injury on MRI. Seizures were most common on the first day, with significant recurrence during and after rewarming. Factors associated with poor outcome on MRI were: high seizure burden, poor aEEG background in first 24 hours, poor aEEG background at 48 hours and 10-minute Apgar score. In multivariate logistic regression, high seizure burden was independently associated with poor MRI outcome (OR 5.00, 95% CI 1.47-17.05 p=0.01); neither aEEG background, nor 10 minute Apgar score were significant in the model.

Conclusions

Electrographic seizure burden is associated with severity of brain injury on MRI in newborns with HIE undergoing therapeutic hypothermia, independent of aEEG background. Seizures are common during cooling, particularly on day one, with a significant rebound on day four.


(1) Rutherford M et al. Lancet neurology. 2010;9(1):39-45.

Abstracts for

Poster Presentations

Title (Upper case)

A COMPARISON BETWEEN A HUMAN MILK ANALYSER AND ESTABLISHED LABORATORY METHODS

FOR MEASUREMENT OF HUMAN MILK MACRONUTRIENT CONTENT


Andrew Cooper1, Catherine Dorrian2, Marianne Barr2. Introduced by Richard Thwaites


Institution(s)

1. Neonatal Intensive Care Unit, Royal Hospital for Sick Children, Glasgow, UK 2. Department of Clinical Biochemistry, Royal Hospital for Sick Children, Glasgow, UK


The nutrient content of mother’s own milk is known to be variable which poses difficulties in the context of

feeding pre term & sick infants. Use of a human milk analyser (Miris AB, Sweden) as an aid to ‘tailored’

fortification of human milk has been proposed by several authors1,2

. The aim of this study was to compare the

Miris Human Milk Analyser (HMA) with established laboratory methods used to measure macronutrient content.


40 samples of donor expressed human milk were obtained within the regional donor milk bank. Each sample

was analysed using the HMA to obtain macronutrient values for fat, protein, lactose and calculated energy

content. In the laboratory, the Lowry method was used to measure milk protein. The Abbott Architect Analyser

was used to measure milk fat. Lactose content was derived from a modification of the method used by Kuhn &

Lowenstein combined with automated analysis. As with the HMA, energy values were calculated.

Results

Measurements for fat and lactose showed excellent correlation between the two methods with correlation

coefficients of 0.97 and 0.96 respectively. Lactose measured by the HMA was slightly lower than by the

laboratory method (mean difference = -0.3g/dL). One sample produced markedly discrepant results for lactose

by the two methods and so was excluded from the correlation analysis. Fat measured by the HMA was slightly

higher than the laboratory method (mean difference = +0.12g/dL). Protein measurements showed a slightly

poorer correlation (r2 0.85), with the HMA producing slightly lower results than the laboratory method (mean

difference -0.31g/dL). For calculated energy, correlation coefficient was 0.92. In this study interassay coefficient

of variance (%CV) for the HMA was, 8.1% for protein, 2.0% for fat, 1.8% for lactose & 1.7% for calculated

energy content (n=7).

Conclusions

The results show a good agreement between the Miris HMA and the standard laboratory methods for all

macronutrient parameters. This makes the HMA a desirable option for rapid assessment of milk nutrient content

in the clinical environment. The potential impact on neonatal nutrition must be further explored.


1.Casadio Y et al. Evaluation of a Mid-Infrared Analyser for the Determination of the Macronutrient Composition of Human Milk. J Hum Lact. (2010) 26(4) 376-83. 2.Menjo A et al. Bedside Analysis of Human Milk for Adjustable Nutrition Strategy. Acta Paed (2009) 98, 380-84

Title (Upper case)

HYPOXIC RESPIRATORY FAILURE IN TERM AND NEAR TERM NEWBORNS: PERSPECTIVE FROM THE NEONATAL TRANSFER SERVICE.


Davidson SL, Ratnavel N, Mohinuddin S, Hird MF, Sinha A.


Institution(s)

The London Neonatal Transport Service, UK. Neonatal Unit of The Children’s Hospital at The Royal London Hospital, Barts Health NHS Trust, London, UK


Transfer for increased level of care of newborns with Hypoxic Respiratory Failure (HRF) is common and can

often be challenging. The data available regarding the transfer of these newborns is limited. Newborns with an

oxygenation index (OI) greater than 25 warrant consideration for Extracorporeal Membrane Oxygenation

(ECMO) in the event of further clinical deterioration, thus affecting the choice of transfer destination. We aimed

to assess the efficacy of management of neonates with hypoxic respiratory failure during inter-hospital transfer

and to identify parameters that predict newborns who will have a persistently high OI.


Retrospective data was collected for all term and near term babies with HRF, who had arterial access at referral,

and were transferred by the London Neonatal Transfer Service over a 7 year period.

Results

83 newborns with HRF were transferred, 8 requiring ECMO. There was no significant difference in median

gestation, birth weight and referral age. Management strategies included; adjustments in ventilation,

administration of surfactant, the use of sedation or paralysis, the initiation of inotropes and the use of inhaled

nitric oxide (iNO). There was no difference between the median FiO2 and mean airway pressure (MAP) from

referral to arrival at destination. However, there was a significant rise in median PaO2 from referral to

destination (Friedman’s ANOVA: χ2=17.9, p<0.01) and a significant reduction in the OI from arrival to departure

(p=0.008). 57 newborns (69%) were commenced on iNO by NTS. There was a significant improvement in

median OI in this group (p=0.008). Logistic regression (forward stepwise method) with OI>25 at departure as

dependent and OI, PIP, MAP, PEEP, PaO2, PaCO2 and pH on the teams arrival as predictors and OI>25 on

teams departure as the dependent variable, showed that only OI at arrival was the only significant predictor.

Using an OI at referral of 22 produced a positive predictive value of 16% with a negative predictive value of

100% for babies who went on to require ECMO.

Conclusions

There was a significant improvement in OI during stabilisation and the transfer. A significant improvement in

arterial oxygenation appears to be associated with iNO being commenced and is unrelated to changes in MAP

and FiO2. The OI on team arrival predicted the likelihood of the OI being greater than 25 at departure but no

other parameters were found to be predictors, consistent with previous studies. The study showed that

discussing cases for ECMO with a OI of 22 picked up all babies that will go onto require ECMO but this meant

discussing 6 babies for every 1 that will go onto need ECMO.

Title (Upper case)

THE EFFECTS OF ANTENATAL STEROIDS ON MORNING CORTISOL AT 7 YEARS OF AGE


Midgley PC, Miller D, Smith J, Yorke J, Armstrong J. (Introduced by Dr Julie-Clare Becher)


Institution(s)

University of Edinburgh, and Lothian University Hospitals NHS Trust.


Antenatal Steroid (ANS) exposure increases offspring BP and alters the hypothalamo-pituitary- adrenal (HPA) axis in many species. There is increasing concern about potential effects of gestational dexamethasone exposure in treatment of CAH. Our hypothesis was that ANS exposure in the context of threatened preterm labour would have programming effects and result in a rise in BP and salivary cortisol in later life. To test this, but avoid the effects of prematurity, this pilot study examined children exposed to ANS who delivered at term.


Subjects were identified by admission at 23-34wks GA with possible preterm labour (abdominal pain,

contractions, bleeding, ?membrane rupture) but delivery 37 weeks GA. Mothers given dexamethasone (ANS

group) and those not (potential control group) were identified from case notes. Comparison was also made with data from healthy schoolchildren studied separately. Measurements were made of BP, salivary cortisol and growth at the age of 7. Local ethics committee approval and informed consent were obtained.

Results

An important finding was the difficulty of identification and recruitment of such cases. 165 children were identified

who had been exposed to ANS. 135 were contacted (27 moved; 2 died; 1 severe CP). 52 ANS exposed children

were recruited, but matched controls could only be recruited for 12 of these. Children were studied at age 6.8-

8.2 years. There were no differences in height weight or BMI between ANS and the school children (or matched

controls). Although systolic and diastolic BP were lower in ANS group than school children, there was no

difference in systolic or diastolic BP between matched controls (n=12) and ANS exposed. ANS children had

normal cortisol diurnal variation, but morning cortisol was lower in ANS group [mean 9.0 (SD 4.7) nmol L-1], than

in in 142 school children [19.2 (15.2) nmol L-1] (p<0.01). Only 3 matched controls provided saliva, but in those

cases morning cortisol was also lower in ANS exposed.

Conclusions

These data show ANS exposure in the context of threatened preterm labour lowers morning cortisol in later life, suggesting these events programme the HPA axis. Since the longterm effects of ANS are unknown, and the study highlights the difficulties of identification, there may be a case for registration of patients exposed to ANS.


Title (Upper case)

BILIOUS VOMITING IN NEWBORNS: IMPLICATIONS FOR A NEONATAL TRANSFER SERVICE


Bhavin Kawa, Syed Mohinuddin, Nandiran Ratnavel, Pankaj Sakhuja, Bernito Bermundo, Harry Ward, Ajay Sinha


Institution(s)

London Neonatal Transfer Service, Barts Health NHS Trust.


Bilious vomiting in a neonate could be a sign of critical intestinal obstruction. As it is difficult to differentiate between those with or without a true underlying surgical problem, neonates presenting with this clinical sign are often transferred to surgical centres for further assessment. Some of these cases may have a time critical pathology. The aim of this study was to evaluate the emergency response to requests for transfer and the clinical outcome of these infants.


A retrospective review of transfers of term babies less than or equal to seven days of age with bilious vomiting between January 2007 and December 2010 to six London neonatal surgical centres was undertaken by The London Neonatal Transfer Service. Cases were identified from the Neonatal Transfer Service database and data were extracted from notes. Follow-up outcome data was collected from all receiving unit hospitals. The study was approved by the local Clinical Effectiveness Unit.

Results

Of 2880 transfers carried out during the review, 163 met the study criteria. The median (range) gestation, birth

weight and age at transfer were.39.9 (37-42) weeks, 3.3(1.8-5.0) kg and 35.3 (2.3 166) hrs respectively. Of

these, 74 (45%) had a surgical diagnosis confirmed. Table below shows the sensitivity, specificity, positive predictive value(PPV) and negative predictive value of abdominal distension, tenderness, feel of abdomen (soft vs firm or tense) and abdominal X-Ray for a diagnosis of surgical condition. Sensitivity (%) Specificity (%) PPV (%) NPV (%)

Abdominal distension 74 44 54 65

Feel of abdomen 11 97 71 63

Abdominal tenderness 62 68 66 64

Abnormal AXR findings 97 14 50 85 Median (IQR) for dispatch of transport team, arrival at referring hospital (response time) were 31 (16-106) minutes and 70 (50-131) minutes respectively. In 34% of transfers dispatch time was longer than 60 minutes. Overall 22/163(14%) of patients transferred for bilious vomiting and 7 of those with dispatch time of greater than 60 minutes had an underlying surgical diagnosis that was time critical in nature.

Conclusions

Bilious vomiting is a clinical sign of underlying surgical pathology in 45% of cases. Abdominal distension and abnormal AXR findings has high sensitivity, whereas feel of abdomen and abdominal tenderness has high specificity for diagnosis of underlying surgical condition. A proportion of surgical diagnoses are time critical and an urgent response to requests for transfer need to be prioritised.

Title (Upper case)

CEASING CPAP AT STANDARD CRITERIA (CICADA): WHY DO INFANTS FAIL TO COME OFF CPAP

IMMEDIATELY.


David A Todd1,2

, Yue Yin1, Audrey Wright

3, Margaret Broom

2, Donna Hovey

4

Abdel-Latif Mohammed1,2

, Bruce Shadbolt1,5

David A Todd1,2


3, Margaret Broom

2, Donna Hovey

4,


, Bruce Shadbolt1,5

David A Todd1,2


3, Margaret Broom

2, Donna Hovey

4,


, Bruce Shadbolt1,5


Institution(s)

1. Australian National University Medical School, Woden, ACT, Australia; 2. Dept Neonatology, Canberra Hospital, Garran,

ACT, Australia; 3. Centre for Newborn Care, Westmead Hospital, NSW, Australia; 4. Grantley Stable NICU, Royal Brisbane

& Women’s Hospital, QLD, Australia; 5. Centre for Advances in Epidemiology & IT, Canberra Hospital Garran, ACT, Australia


We showed in a multicentre RCT (1) that CeasIng Cpap At standarD criteriA (CICADA) compared to cycling off CPAP significantly reduced CPAP weaning time, CPAP time, oxygen requirement, CLD and length of admission. However, some of the premature babies (PBs) using CICADA came off CPAP after 1 or 2 attempts while others required ≥3 attempts. These PBs with ≥3 attempts to come off CPAP had significantly longer CPAP time, and longer oxygen requirements.


This retrospective analysis of the PBs using the CICADA method in the multicentre RCT (1) of PBs <30 weeks gestation compared the diagnosis and outcomes of those who came off in 1-2 attempts (fast group) and those that required ≥3 attempts to come off (slow group).

Results

177 PBs were recruited from April 2006 to October 2009 (1), 50 PBs who ceased CPAP using the CICADA method

completed the trial. The 26 PBs in the “fast group” had a significantly higher gestational age (GA) and birthweight (BWt),

significantly shorter mechanical ventilation (MV), significantly fewer had a patent ductus arteriosus (PDA) compared to the

24 in the “slow group” (table). The “fast group” also ceased CPAP and oxygen at a shorter corrected GA (CGA).

Table: Comparison of fast and slow weaning groups

Fast group (n=26) Slow group (n=24) Sig

GA (weeks)* 27.8±1.4 26.9±1.4 p=0.03

BWt (g)* 1080±249 899±224 p=0.01

Male*** 6 (23.1 %) 10 (41.7 %) NS

Completed Antenatal steroids 19/24 (79.2%) 14 (58.3%) NS

Surfactant 22/24 (91.7%) 24 (100.0%) NS

PDA 5 (19.2%) 13 (54.2%) p=0.02

MV hours** 86±36 260±82 p=0.05

CPAP hours** 213±48 653±67 p<0.001

CGA commencing CPAP* 28.3±1.3 28.4±2.1 NS

CGA ceasing CPAP* 29.5±1.6 32.3±2.0 p<0.001

CGA ceasing oxygen* 29.6±3.3 32.6±3.8 p<0.01

Home oxygen 2 (7.7 %) 2 (8.3 %) NS

*Mean ±1SD, **Mean ±1SE Independent sample t-test, ***Group gender cross tabulation

8

6

±

2

6

0

±

p

=

0

.

Conclusions

PBs with lower GA and BWt in whom the history includes incomplete antenatal steroid coverage, prolonged ventilation with a PDA are less likely to come off CPAP in the first 2 attempts. If PBs fail to come off CPAP after 2 attempts, it may be prudent for them to remain on CPAP for at least another week before trialing off again.


1. Todd et al. Methods of weaning preterm babies <30 weeks gestation off CPAP: A multicentre randomised

controlled trial. Arch Dis Child Fetal Neonatal 2012: Vol 97(4) F236-240.

Title (Upper case)

WHAT PROPORTION OF TRANSFERS IS ‘TIME CRITICAL’ AND ARE WE MOBILISING QUICKLY ENOUGH?


Jenny Rowley1, Mary Pedley

1 and Richard Thwaites

1,2


Institution(s)

1. The Neonatal Unit, Queen Alexandra Hospital, Portsmouth Hospitals NHS Trust, Portsmouth, UK 2. NeTS (Solent), Queen Alexandra Hospital, Portsmouth Hospitals NHS Trust, Portsmouth, UK


NICE quality standard for transfer services (a)1 measures the proportion of teams mobilising to Time Critical

Emergencies (TCEs) <60 minutes from the start of a referring call. Classification of calls is not straightforward2

but national definitions for TCEs have been proposed3. We reviewed our service from April 2012 to March 2013

to estimate the proportion of TCEs, whether we met NICE mobilisation standards and whether there was a difference in mobilisation times between day and night (as this was the first full year of 24 hour operation).


NeTS Solent is the neonatal transfer service covering 9 hospitals in Hampshire, Isle of Wight and parts of West Sussex, Wiltshire and Dorset and sometimes beyond. Transfers are documented on paper with key data entered on an Access® database. The records of all 514 transfers in this 12 months period were reviewed and detailed data was extracted on 156 ‘uplifts’ (Transfers for care that the referring centre does not normally offer

3). Uplifts

were classified as TCEs if they fulfilled national criteria or the baby was passively cooled at the referring unit (agreed in the local neonatal network as TCEs). Some data was missing, mainly on the non-TCE transfers.

Results

There were 93 daytime and 63 night-time uplifts in this 12 month period. Forty one fulfilled TCE criteria (3 with

gastroschisis, 1 Tracheo-oesophageal fistula, 9 intestinal perforations, 1 duct dependent congenital heart defect,

11 with cardio/respiratory instability not responding to treatment and 16 were being passive cooled).

Categories TCE N Mob<60 (%) Non-TCE N Mob<60 (%) TCE v Non-TCE* Missing data

Day 27 20 (74.1) 53 20 (37.7) P=0.0041 13 non-TCE

Night 13 11 (84.6) 44 25 (56.8) P=0.1027 1 TCE + 5 non

Total 40 31 (77.5) 97 45 (46.4) P=0.0012 1 TCE + 18 non

Day=06.00-20.00 hrs, Mob<60=left base<60 min from start of call, * by Fisher’s exact test

Differences between rates of mobilisation in < 60 minutes between day and night calls were not significant. Conclusions

TCEs accounted for 26% of uplifts and 8% of all transfers in this period. Mobilisation times were generally within the NICE standard, with no significant difference between night and day. The proportion of mobilisations to TCEs at <60 minutes was significantly higher than to non-TCE uplifts, suggesting this is a useful classification of calls.


1. Available at: http://publications.nice.org.uk/specialist-neonatal-care-quality-standard-qs4, accessed 1/5/2013, 2. Leslie A & Fenton A, Arch Dis Child F&N 2012;97:1 F77. 3. NTG BAPM National Dataset Review 2012 v3

Self Certificate of Attendance

Please complete the form below and have it signed by a member of the

neonatal society committee if you wish to claim RCPCH CPD points


Pollock Halls, Edinburgh

June 27th – 28th 2013

Name of person claiming CPD points:

(Blockletters)……………………………………….

Place of Work:………………………………………………………………….

Number of CPD points claimed :……………………………………………..

(1 point per hour of attendance – up to a maximum of 5 CPD Points per day)

Claimant’s Signature…………………………..

Name and signature of Neonatal Society Committee member

…………………………………………………………

Helen Budge/Howard Clark/Richard Thwaites/Neena Modi/Matthew Hyde/Jane

Norman/James Boardman (please delete as appropriate)

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